Bacteria Striking Back

Bacterial infections are much less deadly than they used to be before the introduction of antibiotics. “Before we had antibiotics, infections like scarlet fever could even lead to heart problems.

Antibiotic resistance is a growing threat, and new solutions are urgently needed. One promising approach is the development of mRNA vaccines, which have already shown great promise in preventing COVID-19. Now, researchers are using this same technology to create a vaccine against Clostridium difficile (C. difficile), a bacterium that causes severe intestinal infections, especially in hospitalized patients.

C. difficile infections (CDIs) are a major health concern, affecting around 500,000 patients yearly in the USA and causing 30,000 deaths. Another effect of CDIs is that they tend to be re-occurring in 35% of the cases. Among these first re-occurring cases, 60% will re-occur further, potentially turning into a chronic issue.

As CDI affects mostly vulnerable populations, the very young or old people, or seriously sick, this can also reduce their recovery from other health issues. C. difficile spores are also very resistant, making their complete elimination in the environment difficult, especially in hospitals and healthcare centers.

To tackle this issue, researchers used the mRNA-LNP (Lipid NanoParticle) vaccine platform, the same platform that gave us the mRNA COVID-19 vaccines. Contrary to traditional vaccines, mRNA vaccines can train the immune system to target the bacteria in several different ways.

The C. difficile mRNA vaccine was designed to target an enzyme found in diverse strains of this bacterium that processes several surface factors required for gut colonization and virulence. So not only should this help target the bacteria in general, but it should, at least in theory, affect especially the most virulent strains.

When tested in animal models, the experimental vaccine created a strong immune response against all forms of C. difficile, including vegetative cells and spores. The immune response was mediated through long-lived T cells, anti-toxin immunoglobulin G, and mucosal antibody responses.

This allowed for 100% survival of the mice, as well as no measurable impact on the rest of the gut microbiome, increasingly understood as a key factor in maintaining overall health.